263 research outputs found

    Photophysical and Optical Properties of Semiconducting Polymer Nanoparticles Prepared from Hyaluronic Acid and Polysorbate 80

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    Copyright © 2019 American Chemical Society. A nanoprecipitation procedure was utilized to prepare novel diketopyrrolopyrrole-based semiconducting polymer nanoparticles (SPNs) with hyaluronic acid (HA) and polysorbate 80. The nanoprecipitation led to the formation of spherical nanoparticles with average diameters ranging from 100 to 200 nm, and a careful control over the structure of the parent conjugated polymers was performed to probe the influence of π-conjugation on the final photophysical and thermal stability of the resulting SPNs. Upon generation of a series of novel SPNs, the optical and photophysical properties of the new nanomaterials were probed in solution using various techniques including transmission electron microscopy, dynamic light scattering, small-angle neutron scattering, transient absorption, and UV-vis spectroscopy. A careful comparison was performed between the different SPNs to evaluate their excited-state dynamics and photophysical properties, both before and after nanoprecipitation. Interestingly, although soluble in organic solution, the nanoparticles were found to exhibit aggregative behavior, resulting in SPNs that exhibit excited-state behaviors that are very similar to aggregated polymer solutions. Based on these findings, the formation of HA- and polysorbate 80-based nanoparticles does not influence the photophysical properties of the conjugated polymers, thus opening new opportunities for the design of bioimaging agents and nanomaterials for health-related applications

    Augmentative and alternative communication for children with autism spectrum disorder: an evidence-based evaluation of the Language Acquisition through Motor Planning (LAMP) programme

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    Children diagnosed with autism spectrum disorder often have restricted verbal communication. For children who do not use functional speech, augmentative and alternative communication (AAC) devices can be an important support. We evaluated the effectiveness of one AAC programme, the Language Acquisition through Motor Planning (LAMP) using a Vantage Liteâ„¢ device as the speech output in the home and school environments. Eight children with limited communication were assessed by a speech pathologist prior to the introduction of the programme, after five weeks of training and again after a further two weeks of use of the programme, but without the supported training. The pre-/post-assessment measures revealed that all eight children made gains in the development of spontaneous communication using the device during the implementation period. Parents and teachers also reported that the gains achieved during the five-week trial were greater than those achieved in previous interventions. Two years after the completion of the study, a follow-up phone interview was completed which identified that children who received ongoing support from a LAMP-trained speech pathologist continued using the LAMP programme. As a result of this study, a specialised LAMP specific classroom was established in one of the participating schools

    Self-Organization of Anastral Spindles by Synergy of Dynamic Instability, Autocatalytic Microtubule Production, and a Spatial Signaling Gradient

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    Assembly of the mitotic spindle is a classic example of macromolecular self-organization. During spindle assembly, microtubules (MTs) accumulate around chromatin. In centrosomal spindles, centrosomes at the spindle poles are the dominating source of MT production. However, many systems assemble anastral spindles, i.e., spindles without centrosomes at the poles. How anastral spindles produce and maintain a high concentration of MTs in the absence of centrosome-catalyzed MT production is unknown. With a combined biochemistry-computer simulation approach, we show that the concerted activity of three components can efficiently concentrate microtubules (MTs) at chromatin: (1) an external stimulus in form of a RanGTP gradient centered on chromatin, (2) a feed-back loop where MTs induce production of new MTs, and (3) continuous re-organization of MT structures by dynamic instability. The mechanism proposed here can generate and maintain a dissipative MT super-structure within a RanGTP gradient

    Tunable kinetic proofreading in a model with molecular frustration

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    In complex systems, feedback loops can build intricate emergent phenomena, so that a description of the whole system cannot be easily derived from the properties of the individual parts. Here we propose that inter-molecular frustration mechanisms can provide non trivial feedback loops which can develop nontrivial specificity amplification. We show that this mechanism can be seen as a more general form of a kinetic proofreading mechanism, with an interesting new property, namely the ability to tune the specificity amplification by changing the reactants concentrations. This contrasts with the classical kinetic proofreading mechanism in which specificity is a function of only the reaction rate constants involved in a chemical pathway. These results are also interesting because they show that a wide class of frustration models exists that share the same underlining kinetic proofreading mechanisms, with even richer properties. These models can find applications in different areas such as evolutionary biology, immunology and biochemistry

    Prime movers : mechanochemistry of mitotic kinesins

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    Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

    A deterministic oscillatory model of microtubule growth and shrinkage for differential actions of short chain fatty acids.

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    Short chain fatty acids (SCFA), principally acetate, propionate, butyrate and valerate, are produced in pharmacologically relevant concentrations by the gut microbiome. Investigations indicate that they exert beneficial effects on colon epithelia. There is increasing interest in whether different SCFAs have distinct functions which may be exploited for prevention or treatment of colonic diseases including colorectal cancer (CRC), inflammatory bowel disease and obesity. Based on experimental evidence, we hypothesised that odd-chain SCFAs may possess anti-mitotic capabilities in colon cancer cells by disrupting microtubule (MT) structural integrity via dysregulation of β-tubulin isotypes. MT dynamic instability is an essential characteristic of MT cellular activity. We report a minimal deterministic model that takes a novel approach to explore the hypothesised pathway by triggering spontaneous oscillations to represent MT dynamic behaviour. The dynamicity parameters in silico were compared to those reported in vitro. Simulations of untreated and butyrate (even-chain length) treated cells reflected MT behaviour in interphase or untreated control cells. The propionate and valerate (odd-chain length) simulations displayed increased catastrophe frequencies and longer periods of MT-fibre shrinkage. Their enhanced dynamicity was dissimilar to that observed in mitotic cells, but parallel to that induced by MT-destabilisation treatments. Antimicrotubule drugs act through upward or downward modulation of MT dynamic instability. Our computational modelling suggests that metabolic engineering of the microbiome may facilitate managing CRC risk by predicting outcomes of SCFA treatments in combination with AMDs

    Emergent Genome-Wide Control in Wildtype and Genetically Mutated Lipopolysaccarides-Stimulated Macrophages

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    Large-scale gene expression studies have mainly focused on highly expressed and ‘discriminatory’ genes to decipher key regulatory processes. Biological responses are consequence of the concerted action of gene regulatory network, thus, limiting our attention to genes having the most significant variations is insufficient for a thorough understanding of emergent whole genome response. Here we comprehensively analyzed the temporal oligonucleotide microarray data of lipopolysaccharide (LPS) stimulated macrophages in 4 genotypes; wildtype, Myeloid Differentiation factor 88 (MyD88) knockout (KO), TIR-domain-containing adapter-inducing interferon-β (TRIF) KO and MyD88/TRIF double KO (DKO). Pearson correlations computed on the whole genome expression between different genotypes are extremely high (>0.98), indicating a strong co-regulation of the entire expression network. Further correlation analyses reveal genome-wide response is biphasic, i) acute-stochastic mode consisting of small number of sharply induced immune-related genes and ii) collective mode consisting of majority of weakly induced genes of diverse cellular processes which collectively adjust their expression level. Notably, temporal correlations of a small number of randomly selected genes from collective mode show scalability. Furthermore, in collective mode, the transition from large scatter in expression distributions for single ORFs to smooth linear lines emerges as an organizing principle when grouping of 50 ORFs and above. With this emergent behavior, the role of MyD88, TRIF and novel MyD88, TRIF-independent processes for gene induction can be linearly superposed to decipher quantitative whole genome differential control of transcriptional and mRNA decay machineries. Our work demonstrates genome-wide co-regulated responses subsequent to specific innate immune stimulus which have been largely neglected

    A Mechanism for the Polarity Formation of Chemoreceptors at the Growth Cone Membrane for Gradient Amplification during Directional Sensing

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    Accurate response to external directional signals is essential for many physiological functions such as chemotaxis or axonal guidance. It relies on the detection and amplification of gradients of chemical cues, which, in eukaryotic cells, involves the asymmetric relocalization of signaling molecules. How molecular events coordinate to induce a polarity at the cell level remains however poorly understood, particularly for nerve chemotaxis. Here, we propose a model, inspired by single-molecule experiments, for the membrane dynamics of GABA chemoreceptors in nerve growth cones (GCs) during directional sensing. In our model, transient interactions between the receptors and the microtubules, coupled to GABA-induced signaling, provide a positive-feedback loop that leads to redistribution of the receptors towards the gradient source. Using numerical simulations with parameters derived from experiments, we find that the kinetics of polarization and the steady-state polarized distribution of GABA receptors are in remarkable agreement with experimental observations. Furthermore, we make predictions on the properties of the GC seen as a sensing, amplification and filtering module. In particular, the growth cone acts as a low-pass filter with a time constant ∼10 minutes determined by the Brownian diffusion of chemoreceptors in the membrane. This filtering makes the gradient amplification resistent to rapid fluctuations of the external signals, a beneficial feature to enhance the accuracy of neuronal wiring. Since the model is based on minimal assumptions on the receptor/cytoskeleton interactions, its validity extends to polarity formation beyond the case of GABA gradient sensing. Altogether, it constitutes an original positive-feedback mechanism by which cells can dynamically adapt their internal organization to external signals

    Students’ Motivation for Learning in Virtual Learning Environments

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    The specific characteristics of online education require of the student engagement and autonomy, factors which are related to motivation for learning. This study investigated students’ motivation in virtual learning environments (VLEs). For this, it used the Teaching and Learning Strategy and Motivation to Learn Scale in Virtual Learning Environments (TLSM-VLE). The scale presented 32 items and six dimensions, three of which aimed to measure the variables of autonomous motivation, controlled motivation, and demotivation. The participants were 572 students from the Brazilian state of Paraná, enrolled on higher education courses on a continuous education course. The results revealed significant rates for autonomous motivational behavior. It is considered that the results obtained may provide contributions for the educators and psychologists who work with VLEs, leading to further studies of the area providing information referent to the issue investigated in this study
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